Nitrated fatty acids prevent TNFα-stimulated inflammatory and atherogenic responses in endothelial cells

Nitration products (nitroalkenes) of linoleic acid (LNO2) and oleic acid (OA-NO2) can act as endogenous PPARγ ligands with electrophilic properties to exert anti-inflammatory effects on atherosclerotic plaques in the vasculature. Here, we show that OA-NO2 and LNO2 prevent tumor necrosis factor α (TNFα)-stimulated inflammatory and atherogenic responses in human umbilical vein endothelial cells (HUVECs). Both OA-NO2 and LNO2 prevented TNFα-stimulated release of the cytokines, IL-6, IL-8, IL-12/p40, IFNγ, MCP-1, and IP-10, and inhibited NF-κB activation. OA-NO2 and LNO2 also blocked TNFα-induced expression of the adhesion molecules, ICAM-1, VCAM-1, and E-selectin, and suppressed monocyte adhesion to HUVECs. In each case, OA-NO2 was more potent and efficacious than was LNO2, possibly due to increased stability in aqueous media. Collectively, these results substantiate a new functional role for nitrated fatty acids, demonstrating that OA-NO2 and LNO2 exert an anti-inflammatory function against the inflammatory cascade initiated by the representative pro-inflammatory cytokine, TNFα.